Associations ofFTOandMC4RVariants with Obesity Traits in Indians and the Role of Rural/Urban Environment as a Possible Effect Modifier

Abstract

Few studies have investigated the association between genetic variation and obesity traits in Indian populations or the role of environmental factors as modifiers of these relationships. In the context of rapid urbanisation, resulting in significant lifestyle changes, understanding the aetiology of obesity is important. We investigated associations of FTO and MC4R variants with obesity traits in 3390 sibling pairs from four Indian cities, most of whom were discordant for current dwelling (rural or urban). The FTO variant rs9939609 predicted increased weight (0.09 Z-scores, 95% CI: 0.03, 0.15) and BMI (0.08 Z-scores, 95% CI: 0.02, 0.14). The MC4R variant rs17782313 was weakly associated with weight and hip circumference (P < .05). There was some indication that the association between FTO and weight was stronger in urban than that in rural dwellers (P for interaction = .03), but no evidence for effect modification by diet or physical activity. Further studies are needed to investigate ways in which urban environment may modify genetic risk of obesity.

Recent Findings on the Genetics of Obesity: Is there Public Health Relevance?

“…Largescale GWAS in Asian populations have found adiposity hits, which have replicated findings from Europeanbased studies [53,54], and on further investigation, some of the novel hits in these non-western samples also show evidence for association with BMI in European populations, providing a further method of validation for GWAS hits [55,56].…”

Developments in Obesity Genetics in the Era of Genome-Wide Association Studies

“…While the risk allele frequency is higher in Indian Asians (∼40 vs. ∼27% in white Europeans), the effect size on BMI is similar to that observed in white Europeans [36]. Subsequently, this locus has been replicated as an obesity susceptibility locus in other South Asian populations [65,74] and in some studies of populations of African descent [38,75]. Although the risk allele frequency (∼16–20%) in populations of African ancestry was lower, the effect sizes tended to be similar or even somewhat larger than in white Europeans.…”

“…In general, studies in populations of East Asian [48,49,50,51,52,53,54,55,56,57,58,59,60,61,62], South Asian [63,64,65] and African origin [66,67,68,69,70,71,72,73], in particular those with larger sample sizes, have found that the FTO locus associates convincingly with BMI and obesity risk, with effect sizes similar to those observed in white European populations. The risk allele frequency of the FTO locus, however, varies substantially: being ∼20% in East Asian populations, ∼30% in South Asians but ∼45% in white Europeans.…”

Association between FTO, MC4R, SLC30A8, and KCNQ1 gene variants and type 2 diabetes in Saudi population

“…Among the implicated genes include fat mass and obesity associated (FTO) Frayling et al, 2007), melanocortin 4 receptor (MC4R) (Chambers et al, 2008;Loos et al, 2008), solute carrier family 30 member 8 (SLC30A8) (Scott et al, 2007;Sladek et al, 2007;Zeggini et al, 2007), and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) (Unoki et al, 2008;Yasuda et al, 2008). A large number of common genetic variants were found to be associated with obesity phenotypes in western populations (Taylor et al, 2011). Variants in the FTO, MC4R, SLC30A8, and KCNQ1 genes have shown the strongest associations with diabetes and obesity in different populations.…”